The Developmental Therapeutics Program is the keystone of the Karmanos Cancer Institute's effort to develop, understand, and test new treatments for cancer. To achieve this goal the Program is involved in the synthesis of new compounds directed at specific targets as well as the refinement of newly identified compounds. These compounds are initially studied using in vitro systems and animal models prior to testing by our Phase I group. We have developed new agents and approaches that have already entered clinical testing. A second element of the program involves new approaches to understanding and improving tumor response to chemo- and radiotherapy, which includes studies of drug pharmacodynamics and the analysis of pathways of drug metabolism and resistance in normal tissue and tumor samples. The third aim of the program expands the use of new non-invasive imaging approaches (e.g., PET, MRI, ultrasound) that are being developed to measure tumor growth, perfusion, and drug kinetics. Finally, we are validating our new approaches in Phase II and Phase Ill trials. Our faculty conducts this research as part of investigator initiated trials at our institution, as part of multicenter studies, or in national trials through a number of cooperative groups. Each of these main themes brings clinical and basic science researchers together to produce innovative new therapies and means of assessment. Investigators in the Breast, Population Studies and Prevention, Molecular Biology and Human Genetics, and Proteases and Cancer Programs are collaborating in testing new therapeutic approaches along with colleagues in Developmental Therapeutics. Over the last few years a large number of new treatments have been introduced to the clinic, and a larger number are still in the pipeline. This Program is focused on ways to speed the assessment of the promise and pitfalls of each new therapy to ultimately provide patients with the best possible chance at survival.